Antiarrythmics Pharm 7/6/06
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- transmembrane potential is determined by?
- Na, K, and Ca
- molecular gate status controlled by?
-
1) ionic conditions
2) metabolic conditions
3) tranasmembrane voltage - conductance is determined by?
- characteristics of ion channel protein
- current flow = ?
- voltage X conductance
- voltage =?
- actual membrane potential - membrane potential at which no current would flow, even with channels open
-
cardiac action potential
1) phase 0: depolarization -
1) fast upstroke
2) Na channels open (inflow of Na ions)
3) Quinidine blocks Ns current - 2) phase 1: rapid repolarization
-
1) inactivation of Na channels
2) K channels rapidly open and close
3) early repolarizing K current
4) rapidly inactivated
3) open Ca channels - 3) phase 2: plateau
-
1) Ca chennels left open
2) Ca chnnel blockers act here - 4) phase 3: final repolarization
-
1) Ca channels close
2) K channels open (K move to outside) - 5) phase 4: slow spontaneous repolarization
-
1) all the channels are closed
2) resting potential - Na: concentration gradient
-
1) 140 mmol/L outside
2) 10 mmol/L inside - Na: electrical gradient
-
1) 0 mV outside
2) -90 mV inside - driving force of Na?
-
both electrical and concentration
(tending move Na into the cell) - K: concentration gradient
-
1) 4 mmol/L outside
2) 140 mmol/L inside - concentration gradient tends to drive K?
- out
- electrical gradient tends to?
- hold K in
- some K channels ("inward rectifier") are open in the resting state - however, little K current flows because of?
- the balance between the K [ ] and memb. electrical gradients
- cardiac resting membrane potential is mainly determined by?
-
1) extracellular K [ ] and
2) inward rectifier channel state - spontaneous depolarization occurs because?
-
1) gradual > in depolarizing currents
(increaing memb. permiability to Na or Ca)
2) < in repolarizing K currents
(decreasing memb. K permeability) - The maximum upstroke slope of phase 0 is proportional to?
- the Na current
- phase 0 slope is related to?
-
the conduction velocity
(the more rapid the rate of depolarization the greater the rate of impulse propagation) - Phase 2 is the combination of?
- an inward, depolarizing Ca current balanced by an outward, repolarizing K current (delayed rectifier)
- phase 3 is the combination of?
-
Ca and K currents
1) > outward (repolarizing) K current
2) < inward (depolarizing) Ca current - phase 4 in normal His-Purkinje and ventricular muscle cells is characterized by>
-
a balance between
1) outward Na current and
2) inward K current - medications for A-fib?
-
1) Ca channel blocker (Verapamil, Dilt)
2) beta blocker (Propranolol)
3) Digitalis glycosides - Tx/maintenance of normal SR?
-
1) Quinidine
2) Procainamide - management of PSVT?
-
1) vagal maneuver
2) alpha-adrenergic receptor agonist
3) Digoxin
4) drugs that reduce AV transmission - the drugs that reduce AV transmission?
-
1) Adenosine
2) Verapamil
3) Diltiazem
4) Esmolol
5) DC cardioversion - anti-arrythmic drugs may work by?
-
1) suppressing initiation site (automaticity/after-depo.)
2) preventing early or delayed afterdepo.
3) disrupting a re-entrant pathway - automaticity may be diminished by?
-
1) increasing the maximum diastolic memb. potential
2) decreasing the slope of phase 4 depo.
3) increasing AP duration
4) raising the threshold potential - 1) anatomically determined re-entry (WPW) the arrythmia can be resolved by?
- blocking AP propagation
- 2) termination for functional (non-anatomical) reentry circuits?
-
to prolong refractoriness
(ex. Na channel blockers) - Na cahnnel blockers reduce?
- the percentage of recovered channels
- Na channel blocking antiarrythmic drugs are classified as "use-dependent" because?
-
their effectiveness is dependent upon the frequency of channel opening
(they bind to "open" Na channels) - Type 1a: Prototype
-
1) Quinidine
2) slow the rate of AP rise
3) prolong ventricular effective refractory period - Quinidine
-
1) type 1a
2) D-isomer of quinine
3) antimalarial
4) antipyretic - Quinidine: pharmacokinetics
-
1) 80-90% bind to plasma albumin
2) rapid oral absorption
3) No IM
4) limited IV administration - IV administration of Quinidine is limited because?
-
1) myocardial depression
2) peripheral vasodilation - Quinidine is metabolized by?
-
1) liver, hydroxylation to inactive metabolites
2) followed by renal excretion
3) careful in pts with impaired renal/hepatic function - decreased Quinidine blood levels with?
-
1) phenytoin
2) phenobarbital
3) rifampin
(P-450 inducers) -
action of Quinidine?
Quinidine depresses? -
1) ectopic pacemaker activity
2) conduction velocity
3) excitability - Quinidine also slows?
- recovery from Na channel blockade in depolarized tissue
- Quinidine (Na channel blocker) also blocks?
- K channels
- Quinidine's effect on the ECG: QT interval lengthening because?
- Quinidine-mediated reduction in repolarizing outward K current
- Na channel blockade results in?
-
1) an increased threshold
2) decreased automaticity - Quinidine is used for?
-
1) A-fib/A-flutter
2) V-tac
3) PVCs
4) SVT from WPW - Why do you have to give Digitalis prior to Quinidine administration?
-
to prevent paradoxical increase in ventricular response due to Quinidine's vagolytic effect at the AV node
(Digitalis = vagotonic, increase vagal tone at the AV node) - cardiovascular side effects of Quinidine (>2 mcg/ml)?
-
1) > PR, QRS, QT
2) heart block
3) Quinidine syncope
4) hypotension esp. with IV admi.
5) tachycardia
6) Torsades de pointes (> QT) - other adverse effects of Quinidine?
-
1) cinchonism
2) N/V, diarrhea
3) Digitalis toxicity
4) enhance the effect of NMB
5) recurrence of skeletal muscle paralysis post-op - S/S of cinchonism?
-
1) blurred vision
2) decreased hearing acuity
3) GI upset
4) headaches
5) tinnitus - Procainamide: class 1a is used for?
-
1) SVT
2) Vent. arrythmia
3) suppress PVCs - Procainamide is?
- local anesthetic (Procaine) analog
- elimination of Procainamide?
-
1) 40-60 % excreted unchanged (renal)
2) Acetylation (hepatic)
3) highly resistant to hydrolysis by plasma esterases - cardioactivi metabolite of Procainamide?
- NAPA (N-acetylprocainamide)
- NAPA accumulation lead to?
- Torsades de pointes
- Procainamide: the difference compared to Quinidine?
-
1) No vagolytic (antimuscarinic) activity
2) less hypotension (does not block alpha) - side effect from long term use of Procainamide?
-
reversible lupus erythematosus-like syndrome
(25-50 % occurance) - S/S of LE
-
1) serositis
2) arthralgia
3) arthritis
4) pluritis
5) pericarditis
6) parenchymal pulmonary disease - Disopyramide (Norpace): class 1a
-
1) similar to Quinidine
2) greater antimuscarinic effects - Class 1a drugs?
-
1) Quinidine
2) Procainamide
3) Disopyramide (Norpace)